Comparison of Drug Distribution Images from Whole-Body Thin Tissue Sections Obtained Using Desorption Electrospray Ionization Tandem Mass Spectrometry and Autoradiography

Abstract

Desorption electrospray ionization tandem mass spectrometry (DESI-MS/MS) and whole-body autoradiography (WBA) were used for chemical imaging of whole-body thin tissue sections of mice intravenously dosed with propranolol (7.5 mg/kg). DESI-MS/MS imaging utilized selected reaction monitoring detection performed on an AB/MDS SCIEX 4000 QTRAP mass spectrometer equipped with a prototype extended length particle discriminator interface. Propranolol images of the tissue sections using DESI-MS/MS were obtained at surface scan rates of 0.1, 0.5, 2, and 7 mm/s. Although signal decreased with increasing scan rate, useful whole-body images for propranolol were obtained from the tissues even at 7 mm/s, which required just 79 min of analysis time. Attempts to detect and image the distribution of the known propranolol metabolites were unsuccessful. Regions of the tissue sections showing the most radioactivity from WBA sections were excised and analyzed by high-performance liquid chromatography (HPLC) with radiochemical detection to determine relative levels of propranolol and metabolites present. Comparison of the DESI-MS/MS signal for propranolol and the radioactivity attributed to propranolol from WBA sections indicated nominal agreement between the two techniques for the amount of propranolol in the brain, lung, and liver. Data from the kidney showed an unexplained disparity between the two techniques. The results of this study show the feasibility of using DESI-MS/MS to obtain useful chemical images of a drug in whole-body thin tissue sections following drug administration at a pharmacologically relevant level. Further optimization to improve sensitivity and enable detection of the drug metabolites will be among the requirements necessary to move DESI-MS/MS chemical imaging forward as a practical tool in drug discovery.

Fully automated liquid extraction‐based surface sampling and ionization using a chip‐based robotic nanoelectrospray platform

“…Comparisons are made between these data and our reported results analyzing the same samples with the conventional LMJ-SSP [13,14,16] and with a sealing surface sampling probe system (SSSP). [21] Experimental Section Chemicals High performance liquid chromatography (HPLC) grade acetonitrile (ACN), methanol (MeOH) and water were purchased from Burdick & Jackson (Muskegon, MI, USA).…”

“…1). [4 -14] Reported applications of the LMJ-SSP include sampling and analysis of dried drugs or proteins or solutions thereof from wells on microtiter plates, [4] drugs captured in solidphase extraction cards, [6] dyes, inks or pharmaceuticals on paper or separated on hydrophobic reversed-phase (C8 and C18) thin-layer chromatography plates, [5,7 -10] exogenous compounds from thin tissue sections, [13,14] and surface deposited and affinity captured proteins. [12] The LMJ-SSP has also been configured as a twoelectrode electrochemical cell to enable analytically beneficial electrochemically initiated analyte modifications.…”

Technologies for Investigating the Physiological Barriers to Efficient Lipid Nanoparticle–siRNA Delivery

“…3) or siRNA. QWBA is a comprehensive and quantitative method for assessing the tissue distribution of radiolabeled materials in preclinical species (Coe 2000;Kertesz et al 2008). QWBA was used to examine the biodistribution of LNP201-siRNA at various time points by radiolabeling the lipid delivery vehicle, CLinDMA, with 14 C and administering 14 C-LNP201-siRNA to rats intravenously Delivery is the key challenge to be addressed before an siRNA therapeutic can be fully realized.…”

Desorption electrospray ionization mass spectrometry reveals surface-mediated antifungal chemical defense of a tropical seaweed

“…DESI-MS has proven useful in applications such as the analysis of counterfeit drug molecules on intact pharmaceutical tablets (26) and detection of alkaloids from terrestrial plants (27), among others. The potential of DESI-MS imaging has very recently started to be explored in applications including the assessment of lipid and drug spatial distributions in mammalian tissue sections (28)(29)(30)(31). These studies suggest that DESI-MS imaging could be used as a powerful tool in exploring the function of surface-associated natural products in ecological interactions.…”